ORPHA:436159
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
Also known as: ALPS due to CTLA4 haploinsuffiency · CHAI · CTLA-4 haploinsufficiency with autoimmune infiltration disease
Clinical definition (Orphanet)
A rare, primary immunodeficiency characterized by variable combination of enteropathy, hypogammaglobulinemia, recurrent respiratory infections, granulomatous lymphocytic interstitial lung disease, lymphocytic infiltration of non-lymphoid organs (intestine, lung, brain, bone marrow, kidney), autoimmune thrombocytopenia or neutropenia, autoimmune hemolytic anemia and lymphadenopathy.
How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.
Is anyone studying this?
300
300 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=183) is 38.
300 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 38 (publications denominator n=183).
272 in the last 10 years · medium confidence · 83.9th percentile (publications denominator)
Is a treatment being tested?
97
trials for this specific condition
97 interventional trials matched this specific condition name; 32 currently recruiting in our sample. 3 trials are registered for autoimmune lymphoproliferative syndrome, the broader category — shown separately because they may or may not enrol this specific subtype.
Data as of 26 July 2026
3
trials for autoimmune lymphoproliferative syndrome, the broader category this belongs to
Trials registered for a broader category may or may not enrol people with this specific subtype — eligibility criteria vary, and the trial record often doesn't say. Worth raising with a clinician. How we count trials.
97 interventional trials — more than 59.2% of diseases in the trials denominator have none at all (151 of 255; this disease is at the 96.7th percentile).
medium confidence · 96.7th percentile (trials denominator)
Do we know what causes it?
Yes — we know a specific gene responsible (CTLA4).
GenCC classification: Definitive.
Who's working on it?
1,538
Distinct author names in 200 sampled papers — named people below.
Who's working on it?
People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.
- 01Cook MC4 papers · 2023
Department of Immunology and Infectious Diseases, Australian National University, Canberra, ACT, Australia.
Papers in Europe PMC - 02Kanegane H4 papers · 2026
Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Papers in Europe PMC - 03Leavis HL4 papers · 2026
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht and Utrecht University, Utrecht, the Netherlands. h.leavis@umcutrecht.nl.
Papers in Europe PMC - 04Lucas CL4 papers · 2026
Molecular Development of the Immune System Section, Laboratory of Immunology, NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Papers in Europe PMC - 05Tangye SG4 papers · 2026
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Papers in Europe PMC - 06Warnatz K4 papers · 2025
Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Papers in Europe PMC - 07
- 08
- 09Consolini R3 papers · 2025
Section of Clinical and Laboratory Immunology, Division of Pediatrics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Papers in Europe PMC - 10Cornalba M3 papers · 2024
University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy.
Papers in Europe PMC
Recruiting interventional trials
Trials testing a treatment from the matched ClinicalTrials.gov set
97 interventional trials matched after quoted-phrase search and title/condition post-filter.
- NCT04842812·Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors
- NCT07366866·A Study of Safety, Tolerability, PK, and PD of Subcutaneous GenSci136 in Healthy Adults.
- NCT07333118·A Clinical Study to Evaluate the Safety and Efficacy of GT801 Injection in the Treatment of Moderate-to-Severe Refractory Autoimmune Diseases
- NCT06633042·The Safety and Efficacy of Universal CAR-T Cells Targeting BCMA in the Treatment of Refractory NMOSD
- NCT06964269·Use of Acthar Gel Single-Dose Pre-Filled SelfJectTM Injector in Patients With Moderate-Severe Keratitis and Autoimmune Disease
- NCT06792799·Anti-CD19/BCMA CAR-NK Cells in Patients With B Cell Mediated Autoimmune Disease
- NCT06888960·Safety Study of CC312 in Autoimmune Disease Patients
- NCT07085104·A Study to Investigate the Safety and Preliminary Efficacy of ALLO-329, an Allogeneic CAR T-cell Therapy, in Adults With Autoimmune Disease
- NCT06557265·A Phase 1/2 Study of NKX019 in Subjects With Autoimmune Disease (Ntrust-1)
- NCT00977977·Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
- NCT06375993·A Phase 1 Study of Prulacabtagene Leucel (Prula-cel, Formerly ADI-001) in Autoimmune Disease
- NCT06379646·An Clinical Study of YTS109 Cell Injection in Subjects With Recurrent/Refractory Autoimmune Disease
- NCT06983964·Safety and Efficacy of CD19 CAR-T Therapy for Recurrent/Refractory Autoimmune Diseases
- NCT06308978·A Phase 1 Study of FT819 in B-cell Mediated Autoimmune Disease
- NCT06925542·A Safety and Efficacy Study Evaluating CTX112 in Adult Subjects With Refractory Autoimmune Disease
Observational and natural-history studies
44 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.
Recruiting or not-yet-recruiting
- NCT01280825·The 1200 Patients Project: Studying the Implementation of Clinical Pharmacogenomic Testing
- NCT04751396·Testing of an Educational Tool for Patients With Melanoma and Pre-Existing Autoimmune Disease Who Are Candidates for Immune Checkpoint Inhibitors
- NCT06004349·Autoimmune and Autoinflammatory Genetics Study
- NCT06549907·A Biomarker Exploratory Study of Dual Blockade of PD1/PDL1 and CTLA4 and Anti-angiogenic Therapy
- NCT05007340·ILD-SARDs Registry and Biorepository
- NCT03276923·Maternal Autoimmune Disease Research Alliance (MADRA) Registry
- NCT05878964·Evaluation of Skin Health and QoL in Pts Receiving Anti-PD1/PDL1/CTLA4 or CDK Inhibitors.
- NCT06587828·A Biospecimen Collection Study to Identify the Targets of Disease-Reactive T Cells in Patients With Autoimmune Disease
- NCT07249060·Interferon Signature in Anti-CTLA-4 and Anti-PD-1/PD-L1-Treated Cancer Patients Compared With Systemic Autoimmune Disease Patients
- NCT06502015·Biomarkers in Autoimmune Disease of Nervous System
- NCT00943514·Natural History of Bronchiectasis
- NCT06507800·Cancer as a complicATion in reCipients of Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Disease iNdiCation trEated in FRance and Canada?
- NCT02257892·Novel Genetic Disorders of the Immune System
- NCT05204459·MS-ResearchBiomarkerS
- NCT05842824·An Observational Study of Patients With Autoimmune Disease
Where to find support
We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:
India — NPRD
Last verified 2026-07-26This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.
Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.
How we counted this
Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored below but are not added to the query string.
"Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency" OR "ALPS due to CTLA4 haploinsuffiency" OR "CTLA-4 haploinsufficiency with autoimmune infiltration disease" OR "ALPS due to CTLA4 haploinsufficiency" OR "ALPS type 5" OR "ALPS type V" OR "CTLA4 haploinsufficiency" OR "autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency" OR "autoimmune lymphoproliferative syndrome type 5" OR "autoimmune lymphoproliferative syndrome type V" OR "immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation"
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency" OR "ALPS due to CTLA4 haploinsuffiency" OR "CTLA-4 haploinsufficiency with autoimmune infiltration disease" OR "ALPS due to CTLA4 haploinsufficiency" OR "ALPS type 5" OR "ALPS type V" OR "CTLA4 haploinsufficiency" OR "autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency" OR "autoimmune lymphoproliferative syndrome type 5" OR "autoimmune lymphoproliferative syndrome type V" OR "immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation" OR "CTLA4" OR "autoimmune disease"
Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).
Study-type breakdown: 97 interventional · 44 observational · 0 expanded access. Only interventional studies enter the trial headline.
Cross-references (from Mondo): OMIM:616100 UMLS:C4015214 NCIT:C126341
Query health: ok — strategies attempted: phrase, recall-expansion; with hits: phrase, recall-expansion
Run this search on ClinicalTrials.gov
Synonyms dropped by stoplist: CHAI
Confidence reasoning
- Preferred label is multi-word and distinctive
- 1 synonym(s) dropped by stoplist (may under-count)
- No label/synonym collisions with other diseases in this corpus